The long-term goal of the research is to determine the influence of endothelium on arterial and venous smooth muscle function within the pulmonary vascular bed, and how endothelium-vascular smooth muscle interactions, or aberrations in these interactions, may be involved in the changes which occur in the pulmonary circulation under physiological and pathophysiological conditions. The immediate objective of the presently proposed research is to continue and expand our ongoing investigation of the influences of endothelium on vasoreactivity of pulmonary arteries and veins in vitro, and to further develop our studies into the mechanisms whereby such interactions occur. The specific aims of the research are based upon results previously reported by others as well as those obtained in our laboratory using bovine intrapulmonary arteries and veins. Using in vitro techniques, experiments will be conducted to: 1. demonstrate the existence and investigate the nature of potential contractile factor(s) which may be released from endothelium in bovine intrapulmonary artery and vein; 2. determine the influence of endothelium on effects of hypoxia in bovine intrapulmonary artery and vein; 3. determine if endothelium- smooth muscle interactions observed in bovine intrapulmonary vessels are similar in rat pulmonary vessels; 4. determine if endothelium-smooth muscle interactions observed in bovine intrapulmonary artery and vein are unique or are similar to those which occur in systemic arteries and veins from the same species; and, 5. evaluate and compare the potential of endothelium to release vasoactive substances using bioassay and cultures of bovine pulmonary and mesenteric arterial and venous endothelial cells. The information attained from the experiments will provide additional, basic information necessary for an increased understanding of both the physiological regulation of the pulmonary vascular bed and the pathophysiological changes which occur in the pulmonary circulation in various disease states. Hopefully, an improved understanding of the endothelium-vascular smooth muscle interactions which occur in lung will lead ultimately to more effective therapy of diseases which involve aberrations in the pulmonary circulation.